Anti-TNF drugs (adalimumab, certolizumab, etanercept, golimumab, infliximab) are commonly used with methotrexate (MTX) in rheumatoid arthritis (RA). Despite the development of these new and exciting biological therapies for the treatment of RA, their relatively high costs (<$24,000/year) and possible toxicities (infection, cancer risk, injection site problems) are drawbacks to their use. MTX remains an anchor drug for RA therapy;however, there is substantial unexplained variation in patient response to MTX therapy. It is unknown if anti- TNF drugs may ultimately be discontinued in individuals on dual therapy. The ability to taper an anti-TNF drug may depend on the ability to optimize MTX therapy or the addition of an additional disease modifying antirheumatic drugs (DMARD). We propose a clinical trial planning grant to convene an expert panel to refine the study design, outcome measures, data collection and data analysis for the TAKEOFF Trial (Optimizing Methotrexate and Discontinuing Anti-TNF Agents in RA). This study will test the hypothesis that among patients who have been in clinical remission (CDAI d 2.8) for at least 6 months, patients randomized to discontinue or reduce the dose of anti-TNF therapy with either concomitant optimization of MTX or addition of SSZ + HCQ will have a likelihood of continued remission that is non-inferior compared to patients randomized to continue anti-TNF therapy + MTX. The clinical trial planning process will involve experts related to RA trials planning, MTX biochemistry, outcome measures and data analysis. It is expected at the end of the planning process that an NIH grant will be submitted related to optimization discontinuing biological therapies.